Primary localized cutaneous lichen myxedematosus with light chain-restricted plasma cells: A distinct variant of the localized form of lichen myxedematosus.

Lichen myxedematosus (LM) is a chronic cutaneous mucinosis that can present as a localized skin lesion or as a generalized systemic disease termed scleromyxedema. The differential diagnosis is determined by a combination of clinical presentation, serological studies, and histopathological examination. Currently, well-established and accepted histopathological features to distinguish localized LM from scleromyxedema have not been elucidated. Our recent publication, together with a retrospective literature review, suggests that the presence of groups of light chain-restricted plasma cells represents a distinct histopathological clue for the diagnosis of localized LM. In this report, we provide two additional cases of localized LM with lambda light chain-restricted plasma cells, together with clinical and histopathological findings that are similar to our previous publication. These cases support our theory that the light chain-restricted plasmacytic microenvironment is primarily attributed to the pathogenesis of localized LM. Therefore, we consider these cases to constitute a clinically and pathologically new variant of localized LM and name it primary localized cutaneous LM with light chain-restricted plasma cells.

Resolved Peristomal Erosive Papulonodular Dermatitis Mimicking Nevoid Hyperkeratosis of the Nipple and Areola.

Introduction: Nevoid hyperkeratosis of the nipple and areola (NHKNA) is a rare cutaneous entity with a distinct clinical and histological presentation. The type II form of this condition can result from various dermatoses, such as irritant contact dermatitis. Erosive papulonodular dermatitis is a chronic irritant dermatitis that often occurs in areas of occlusion and maceration, such as peristomal skin. Pseudoverrucous papules and nodules are a variant of erosive papulonodular dermatitis and have a non-specific histologic pattern of reactive hyperplasia. Case Presentation: We present a case of a patient with resolved peristomal erosive papulonodular dermatitis who presented status-post ileostomy reversal with clinical and histologic findings classically seen in NHKNA. Conclusion: In type II NHKNA, treatment of the primary dermatosis typically leads to resolutions. In the case of our patient, removal of the offending agent via colostomy reversal and barrier protection led to the resolution of the lesions.

Spindle Cell Lipoma With Florid Primary Follicular Lymphocytic Hyperplasia: A Novel Association With Potential Diagnostic Pitfalls.

ABSTRACT: Spindle cell lipoma (SCL) is a benign subcutaneous lipomatous neoplasm with a heterogeneous histologic appearance that varies greatly depending on the amount of fat, collagen, and myxoid stroma, which define the multiple subtypes of SCL, such as fat poor SCL, pseudoangiomatous SCL, and dendritic fibromyxolipoma. Cutaneous lymphoid hyperplasia is a spectrum of benign conditions characterized by reactive B-cell and T-cell cutaneous lymphocytic infiltrates. Cutaneous B-cell lymphoid hyperplasia is a heterogeneous group of non-neoplastic conditions that can be observed as reactive phenomena to infections, medications, allergens, or neoplasms and must be distinguished from cutaneous B-cell lymphomas. Here, we report a novel case of spindle cell lipoma, associated with B-cell primary lymphoid follicular hyperplasia, mixed within the tumor in a peculiar pattern, while discussing potential diagnostic pitfalls with low-grade B-cell lymphomas. This is the first report of such association in the literature.

Congenital Giant Juvenile Xanthogranuloma, Let It Be.

Description Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. JXGs are benign and have a self-limiting course generally lasting 6 months to 3 years, with some reported durations longer than 6 years. We present a rarer congenital giant variant, defined as lesions with a diameter larger than 2 cm. It is uncertain if the natural history of giant xanthogranulomas is similar to the usual JXG. We followed a 5-month-old patient with a 3.5 cm in diameter, histopathologically-confirmed, congenital, giant JXG located on the right side of her upper back. The patient was seen every 6 months for 2.5 years. At 1 year of age, the lesion had decreased in size, lightened in color, and was less firm. At 1.5 years old, the lesion had flattened. By 3 years old, the lesion had resolved but left a hyperpigmented patch with a scar at the punch biopsy site. Our case represents a congenital giant JXG that was biopsied to confirm the diagnosis and then monitored until resolution. This case supports the clinical course of giant JXG not being affected by the larger lesion size and that aggressive treatments or procedures are not warranted.

Recurrent Granuloma Gluteale Infantum Secondary to Fecal Overflow Incontinence.

Granuloma gluteale infantum is a rare pediatric dermatological disorder of uncertain etiology. Suggested causes include fluorinated corticosteroids, Candida albicans, and irritant contact dermatitis. We present the case of a 3-year-old boy with recurrent episodes of granuloma gluteale infantum which resolved with treatment of his fecal overflow incontinence. As each recurrence correlated with a relapse of overflow incontinence, in this case the cause was irritant contact dermatitis from the liquid stool. This is the first reported case of recurrent granuloma gluteale infantum.

Specific TCR gene rearrangements in mycosis fungoides: does advanced clinical stage show a preference?

AIMS: The relationship between the presence of specific T-cell receptor (TCR) gene rearrangements and clinical stage in mycosis fungoides (MF) has not been studied. We analysed a cohort of patients with a diagnosis of MF to determine the different types of specific TCR gene rearrangements present and their relationship to disease stage. METHODS: A retrospective chart review was used to select patients with a diagnosis of MF who had a skin biopsy and a positive TCR gene rearrangement study in either blood or tissue and at least 2 years of clinical follow-up. RESULTS: 43 patients were identified and divided into two groups. The first group consisted of 23 patients with early stage disease (IA-IIA) that was either stable or went into partial or complete remission with minimal intervention. None of these patients advanced to late stage disease. The second group consisted of 20 patients who had either late stage disease at diagnosis or progressed to late stage disease at some point in time. In the first group, only 4/23 (17%) patients had a single TCR gene rearrangement in the VÉ£1-8 region. In contrast, the second group had 13/20 (65%) patients with a single TCR gene rearrangement in the VÉ£1-8 region (p=0.002). CONCLUSION: The presence of a single TCR gene rearrangement in the VÉ£1-8 region could possibly be related to a more advanced stage of MF. However, more comprehensive studies, such as next generation sequencing, with a larger cohort is necessary for a more definitive conclusion.

Livedoid Vasculopathy Presenting in a Patient With Sickle Cell Disease.

We report a case in which a 43-year-old African American male with medical history of sickle cell disease (SCD) presented with a nonhealing ulcer. Biopsy revealed features of livedoid vasculopathy. Previously, livedoid vasculopathy had only been described in a patient with sickle cell trait, but never in a patient with SCD. Livedoid vasculopathy most commonly affects the distal lower extremities and is characterized by irregular, punched-out, painful ulcers that heal with stellate white scars of atrophie blanche. Histologically, it reveals segmental hyalinizing vessels, focal thrombosis, and endothelial proliferation. The etiology is currently unclear, but it has been shown to be related to procoagulant states and a diagnosis of livedoid vasculopathy should prompt a thorough hypercoagulable workup, including testing for SCD in high-risk patients.

Histopathological changes in morphea and their clinical correlates: Results from the Morphea in Adults and Children Cohort V.

BACKGROUND: Histopathological features in morphea (localized scleroderma) and their clinical correlates are poorly described. OBJECTIVE: We sought to systematically describe histologic changes of morphea in a large, well-annotated cohort and determine the association between histopathology and clinical features. METHODS: This was a cross-sectional study of 83 patients enrolled in the Morphea in Adults and Children cohort. The main outcome measure was the association of microanatomical location and degree of sclerosis and inflammation seen on histologic samples with patient-reported symptoms and physician-based measures of severity. RESULTS: Pattern of sclerosis was associated with morphea subtype, the presence of patient-reported symptoms, and functional limitation. A bottom-heavy pattern of sclerosis was associated with pain and tightness (P = .0039 and .001, respectively). These symptoms were not associated with a top-heavy pattern. Severe inflammation may be associated with pain and functional limitation (P = .073 for both). LIMITATIONS: Small sample size limits ability to detect associations, particularly in subgroups. CONCLUSIONS: Histopathological examination of morphea may assist in identifying patients who may require additional monitoring and treatment. Features such as patterns of sclerosis and severity of inflammation should be included in pathology reports to help aid in clinical management.

Perianal Comedones: A Rare Incidental Finding.

Comedones occur when an overproliferation of keratinocytes blocks sebum secretion in a pilosebaceous duct. Comedones have multiple possible etiologies and contributing factors. While comedones are common to acne, they are also seen in occupational exposures and are associated with certain syndromes. We describe a particularly rare case of comedones at the perianus that is not associated with any known exposure or disease and is a rare incidental finding.

Langerhans cell sarcoma with lineage infidelity/plasticity: a diagnostic challenge and insight into the pathobiology of the disease.

Langerhans cell sarcoma is a very rare and aggressive tumor of Langerhans cell lineage, for which aberrant expression of T-cell-related antigens has not yet been reported in a primary skin tumor. The authors describe the first known case of a primary cutaneous Langerhans cell sarcoma with lineage infidelity and use comparative genomic hybridization to investigate the genetic composition of the tumor and detect DNA copy number alterations throughout its entire genome. The case involves a 62-year-old woman who presented with an irregular nodule on the forehead surrounded by smaller lesions in its vicinity. The clinical impression was melanoma with satellitosis. The biopsy specimen showed an epidermotropic tumor with moderate-to-marked cellular pleomorphism and significantly increased mitotic rate but no necrosis. The immunoprofile of the lesion was remarkable, as next to common Langerhans cell markers: Langerin, CD1a, S100, and CD4; it also exhibited an aberrant T-cell phenotype with the expression of CD2, CD3, and CD43. In addition, fascin and CD30 were also expressed, further exaggerating potential diagnostic pitfalls. Langerhans cell lineage was confirmed by the demonstration of characteristic Birbeck granules on electron microscopy. Whole genome analysis for copy number changes and loss of heterozygosity showed a complex karyotype with variable hyperdiploidy and numerous allelic imbalances. Significant findings included a homozygous deletion at 9p21 involving the CDKN2A and loss of heterozygosity at 17p involving TP53 gene, coupled with a TP53 missense mutation. Despite reexcision and multiagent systemic chemotherapy, the patient died of metastasis 2 years after diagnosis. This case is an outstanding example of lineage infidelity in a hematologic malignancy and the utilization of comparative genomic hybridization in characterizing its genetic abnormalities.

Characterization of tissue and slide artifacts from automated embedding systems.

With recent technological advances and cost reductions, automated embedding systems are rapidly becoming routine in the processing of skin biopsy specimens. The efficiency advantages of this technique are due in part to the use of patented sectionable cassettes that hold formalin-fixed tissue from the time of grossing through tissue sectioning. In this process, the final paraffin block contains both the tissue and the cassette, which are sectioned and stained in unison. Here, we report the multiple tissue and slide artifacts commonly seen with automated embedding systems that are unique to this method of tissue processing. The most frequently observed tissue changes are patterned molding of the biopsy specimen around the cassette material. The most common slide artifacts are due to the presence of geometrically shaped polarizable cassette material adjacent to or overlying the stained tissue. As many of these artifacts strongly resemble the shapes seen in the classic 1980s video game, Tetris, we propose the term of Tetris-like artifacts for these findings. Although we remain confident that use of an automated embedding system does not decrease diagnostic reliability, increased familiarity with the standard appearance of slides processed using this technique will help avoid confusion when evaluating these cases.

Defining early mycosis fungoides: validation of a diagnostic algorithm proposed by the International Society for Cutaneous Lymphomas.

BACKGROUND: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma and is often difficult to diagnose. Early-stage disease is particularly challenging and requires clinical and histopathologic correlation to make an accurate diagnosis. In order to facilitate the diagnosis of early MF, an algorithm has been proposed by the International Society for Cutaneous Lymphomas (ISCL) whereby clinical and histopathologic characteristics as well as immunohistochemistry and T-cell receptor gene rearrangement studies may be applied to suspected cases of MF. The diagnostic utility of this algorithm has not yet been validated. We sought to determine the validity of the proposed algorithm via an investigator-blinded, retrospective, case-control study. METHODS: A total of 34 cases were randomly selected from the database of a clinic for cutaneous T-cell lymphomas and included patients with MF and patients with clinicopathologic mimics. The proposed diagnostic algorithm was systematically applied to the entire cohort. Each case was assigned a composite score based on the parameters in the proposed algorithm. RESULTS: Among the 24 cases of MF, 21 cases achieved four or more points through application of the algorithm. Among the 10 cases of MF mimics, only four achieved four or more points. This difference was significant (Fisher's exact test, p = 0.009). The sensitivity of the 4-point threshold for a diagnosis of MF was 87.5% and the specificity was 60%. CONCLUSIONS: The diagnostic algorithm proposed by the ISCL is a statistically valid method for defining cases of early MF and distinguishing these cases from other benign dermatoses. However, the clinical utility of the algorithm may be limited by its low specificity. Further refinement of the algorithm may improve its accuracy.

Site-specific analysis of inflammatory markers in discoid lupus erythematosus skin.

Prior studies identified T cells, B cells, and macrophages in the inflammatory infiltrate and up-regulation of their protein products in discoid lupus erythematosus (DLE) skin; however, they lacked rigorous analyses to define their specific locations in skin. Thus, we compared expressions of selected T cell, B cell, and macrophage markers in five areas of DLE, psoriasis, and normal skin. Immunostainings for CD3, CD4, CD8, CD20, CD68, CXCR3, CXCL10, and TIA-1 were performed in biopsies of 23 DLE lesional skin, 11 psoriasis lesional skin, and 5 normal skin. Three independent observers used a graded scale to rate each marker's presence in the epidermis, dermatoepidermal junction (DEJ), perivascular area, periadnexal area, and deep dermis. DLE lesional skin contained an increased abundance of CD3(+), CD8(+), and CD68(+) cells at the DEJ, and CD20(+) and CD68(+) cells in the periadnexal area versus psoriasis and normal skin. CXCR3, CXCL10, and TIA-1 were elevated in periadnexal sites of DLE lesional skin versus psoriasis lesional skin. The aggregation of T cells, B cells, macrophages, and their protein products (CXCR3, CXCL10, and TIA-1) in the DEJ and periadnexal area of DLE lesional skin may contribute to the pathology of DLE through a coordinated, sophisticated process.

Primary milia localized to the vulva.

Multiple primary milia were found on the vulva of a 52-year-old woman who was referred to the dermatology clinic by her gynecologist. These lesions are commonly distributed on the face and rarely occur in this location without antecedent trauma. This report demonstrates the unique presentation of primary milia in the genital region and explores the diagnostic features and treatment methods of these lesions.

Biomarker evaluation of face transplant rejection: association of donor T cells with target cell injury.

This series of 113 sequential biopsies of full facial transplants provides findings of potential translational significance as well as biological insights that could prompt reexamination of conventional paradigms of effector pathways in skin allograft rejection. Serial biopsies before, during, and after rejection episodes were evaluated for clinicopathological assessment that in selected cases included specific biomarkers for donor-versus-recipient T cells. Histologic evidence of rejection included lymphocyte-associated injury to epidermal rete ridges, follicular infundibula, and dermal microvessels. Surprisingly, during active rejection, immune cells spatially associated with target cell injury consisted abundantly or predominantly of lymphocytes of donor origin with an immunophenotype typical of the resident memory T-cell subset. Current dogma assumes that skin allograft rejection is mediated by recipient T cells that attack epidermal targets, and the association of donor T cells with sites of target cell injury raises questions regarding the potential complexity of immune cell interactions in the rejection process. A more histopathologically refined and immune-based biomarker approach to assessment of rejection of facial transplants is now indicated.

Treatment of high-grade anal intraepithelial neoplasia with infrared coagulation in a primary care population of HIV-infected men and women.

BACKGROUND: High-grade anal intraepithelial neoplasia, the putative anal carcinoma precursor, is more common in HIV-infected persons. The ideal treatment for these lesions has not been established. OBJECTIVE: The aim of this study was to evaluate the effectiveness of infrared coagulation treatment for high-grade anal intraepithelial neoplasia. DESIGN: This is a prospective cohort study. Patients with high-grade anal intraepithelial neoplasia either received infrared coagulation treatment or voluntarily did not receive treatment and were reevaluated at a subsequent time point. SETTING: This investigation was performed at a Ryan White-funded clinic located in the United States. PATIENTS: HIV-infected men and women with biopsy-confirmed high-grade anal intraepithelial neoplasia were included. MAIN OUTCOME MEASURES: The primary outcome measured was the histology collected by high-resolution anoscopy-directed biopsy. RESULTS: The study included 124 patients. Of 42 patients who either delayed treatment or were not treated, 37 (88%; 95% CI = 74%-96%) still had high-grade anal intraepithelial neoplasia on reevaluation and 2 (5%; 95%CI = 1%-16%) had squamous-cell carcinoma. Of 98 patients who received infrared coagulation treatment, 73 (74%; 95% CI = 65%-83%) patients had no evidence of high-grade anal intraepithelial neoplasia on their first posttreatment evaluation, and none had progressed to squamous-cell carcinoma (p < 0.0001 in comparison with untreated). Upon completing all initial and, if necessary, follow-up treatment, 85 (87%; 95% CI = 78%-93%) patients treated by infrared coagulation had no evidence of high-grade anal intraepithelial neoplasia and none had progressed to squamous-cell carcinoma. LIMITATIONS: The study population may not be representative of the general population, the study environment was uncontrolled, and patients were not randomly assigned to treatment. CONCLUSIONS: Infrared coagulation is an effective treatment for high-grade anal intraepithelial neoplasia.